Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1.
Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1.
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DOI：
10.1056/nejmoa1612197
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发表时间：
2017-03-23
期刊：
影响因子：
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通讯作者：
Holland SM
中科院分区：
文献类型：
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作者：
Moutsopoulos NM;Zerbe CS;Wild T;Dutzan N;Brenchley L;DiPasquale G;Uzel G;Axelrod KC;Lisco A;Notarangelo LD;Hajishengallis G;Notarangelo LD;Holland SM
1例白细胞粘附缺陷1型（LAD 1）患者患有严重牙周炎和顽固性、深部、不愈合的骶骨伤口。我们以前发现了一个占主导地位的白细胞介素-23-白细胞介素-17签名在发炎的网站在人类与LAD 1和小鼠模型的疾病。在小鼠模型中阻断这一途径导致免疫病理学状况消退。我们用乌司奴单抗治疗我们的患者，乌司奴单抗是一种结合白细胞介素-23和白细胞介素-12的p40亚基的抗体，从而阻断这些细胞因子的活性，抑制白细胞介素-23依赖性白细胞介素-17的产生。经过1年的治疗，我们的病人有解决他的炎症病变没有严重感染或不良反应。白细胞介素-23和白细胞介素-17的抑制可能在LAD 1的管理中发挥作用。（由国家过敏和传染病研究所和其他机构资助。
A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23–interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23–dependent production of interleukin-17. After 1 year of therapy, our patient had resolution of his inflammatory lesions without serious infections or adverse reactions. Inhibition of interleukin-23 and interleukin-17 may have a role in the management of LAD1. (Funded by the National Institute of Allergy and Infectious Diseases and others.)